Patent GB-1021523-A (GB)
Title: 9-aminoalkyl and 9-aminoalkylidene derivatives of acridan
IPC: C07D219/06
Filed: 1963-06-06
Abstract: The invention comprises compounds of the general formulae <FORM:1021523/C2/1> <FORM:1021523/C2/2> wherein R1 represents a hydrogen atom or a methyl group, R2 represents a hydrogen atom, a halogen atom with an atomic weight of less than 80, a lower alkyl, lower alkoxy, trifluoromethyl, trifluoromethylsulphonyl, dimethylsulphamoyl or lower alkylthio group; R3 represents a lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl lower alkyl, phenyl or phenyl lower alkyl group; R4 represents a hydrogen atom, lower alkyl, lower alkenyl, lower alkynyl, cyclo alkyl-lower alkyl, phenyl, phenyl lower alkyl, lower alkanoyl, benzoyl, carbamoyl or carbalkoxy group and Z represents a di-lower alkylamino, mono-lower alkylamino, N-pyrrolidinyl, N - piperidinyl, N1 - lower alkyl - N - piperazinyl, N1 - hydroxy alkyl - N - piperazinyl, N1 - acetoxyalkyl - N - piperazinyl, N1 - carbamoylox alkyl - N - piperazinyl, N1 - di - lower alkylcarbamoyl oxy alkyl - N - piperazinyl,N1-hydroxy alkyloxy alkyl - N - piperazinyl, N1-hydroxyalkyloxy alkyloxy alkyl - N - piperazinyl groups, and pharmaceutically acceptable acid addition. Salts thereof, wherein lower alkyl and alkoxy groups have 1 to 4 carbon atoms, lower alkanoyl groups and the alkylene portions of substituted alkyl piperazyl radicals have 2 to 4 carbon atoms, and cycloalkyl, lower alkenyl and lower alkynyl groups have 3-6 carbon atoms.  Compounds of the Formula I may be prepared by dehydrating compounds of the formula <FORM:1021523/C2/3> where Z represents a di-lower alkylamino, mono-lower alkylamino, N-pyrrolidinyl, N-piperidinyl, N1 - lower alkyl - N - piperazinyl, or N1 - benzyloxy alkyl - N - piperazinyl radicals.  Compounds of the Formula II may be prepared by reduction of the appropriate compound of the Formula I. Where R4 represents a hydrogen atom, compounds of the Formula II may be prepared by reaction of an acridine of the formula <FORM:1021523/C2/4> with a compound of the formula ZCH2CH(R1)CH2MgX where X represents a halogen atom and Z represents a di-lower alkylamino, N-pyrrolidinyl, N - piperidinyl or N1 - benzyloxyalkyl-N-piperazinyl group, followed by hydrolysin. Compounds of the Formula II, where R4 represents a hydrogen atom and Z represents a mono-lower alkylamino group may be prepared by reacting an acridine with a N-lower alkyl-N-benzylaminopropyl magnesium halide, hydrolysing the product and removing the N-benzyl substituent from the resulting 9-(N-lower alkyl-N - benzylaminopropyl) - 10 - unsubstituted acridine.  10-Lower alkanoyl-, 10-benzoyl-, 10 - carbamoyl - and 10 - carbalkoxy acridans of the Formula II may be prepared by reacting this corresponding 10-unsubstituted acridan with the appropriate halide.  Compounds of the Formulae I and II may be prepared, where Z represents N1 - hydroxy alkyl - N - piperazinyl groups, by hydrolysis of the corresponding N1-benzyloxyalkyl - N - piperazinyl derivative; where Z represents N1-acetoxy alkyl- and N1-di-lower alkylcarbamoyloxyalkyl - N - piperazinyl groups, by reaction of the corresponding N1 - hydroxyalkyl - N - piperazinyl derivative with the appropriate acetyl or carbamoyl halide; and where Z represents N1-hydroxyalkyloxyalkyl - N - piperazinyl or N1 - hydroxyalkyloxy alkyloxyalkyl - N - piperazinyl groups, by converting the corresponding N1-hydroxyalkyl - N - piperazinyl compound into its p-tosylate ester and reacting this ester with the sodium derivative of the appropriate alkylene glycol or dihydroxy alkylene ether. 9-(N1 - Hydroxyalkyl - N - piperazinyl) alkylacridans of the Formula II may be prepared by catalytic hydrogenation of the appropriate 9-(N1 - benzyloxyalkyl - N - piperazinyl) alkylidene acridan. Compounds of the Formulae I and II when Z represents a N1-carbamoyloxyalkyl-N-piperazinyl group may be prepared by the action of liquid ammonia on the phenylcarbonate salt of the corresponding N-hydroxyalkyl - N - piperazinyl compound, prepared by the action thereon of phenyl chlorocarbonate.  Thereapeutic Compositions with tranquillizing, ataractic, antidepressant, antiemetic, antihistaminic, antispasmodic and anti-inflammatory properties comprise compounds of the Formulae I and II, or their pharmaceutically acceptable acid addition salts (including those with ascorbic, salicylic, aspartic, glutamic and theophyllineacetic acids and with 8-halotheophyllines), with a pharmaceutically acceptable carrier or diluent therefor.